Compounds with the carbon skeleton of beta-carotene and process for the manufacture thereof



Patented Sept. 2 1952 ii I UNITED- T ES P T-' omcExi' COMPOUNDS WITH THE cAREoN sKELEToN:

0F BETA-CAROTENE AND rnocEss FOR THE MANUFACTURE THEREOF Hans Herloff Inhoffen and Horst Pornmeifl'f I I Fh e many v. V

i No Drawing. Application May 1 1, 1951; Serial No. 226,944. I n-Germany- M a 3 24 -1950 4 Claims. (01. zen-tiny The present inyention relates to the manufacture 'of a 'novel' condensation product with CH2 H3O According to the present invention, this compound can be prepared by condensing 4- [2',6 ,6'-'

trimethylcyclohexane (1') a yll 2 methylbutene-(2) -al-(1) with a compound of the general formula wherein X stands for a lithium radical or a magnesium-bromide radical; and hydrolyzing the resulting salt of the general formula HsC- CH3 1 ?X I Q}; I.. .I I

0112-011:c-cH-czc-c=cH-0HzoH2-cH=cCEUJnPCQJ H CH: CH: CH: H3 -CH3 113C The course of the new process, when using,

forinstance, the lithium compound of 3,8-dilfiydmlysis methyldecadiene-(3,7)-diyne-(1,9) as starting 3 material, can be illustrated by the following H3O CH3 formula scheme: i I v V t I Hs (llHs oH;cH=c-cH-cEo-c=o11 HsC OH a r CH3 CH3 i I OH CH=CCHO+LiC=O- =cH. I I CH3 I II I II LE2 II CH8 I OH LE2 H3O OH: I I cH, cH c-( H-o- -o =CH 40 0118 Ha CH-CH=C-CHO maze-o: H (3H3 CH9 'Ifhecompound obtainedaccordlng to the presentfl invention is a valuable intermediate prodloondensmon uct for the preparation of biologically active sub- HIC CHI I I stances of the kind of B-carotene. Y I 3, CH3 The starting materials of the process may be obtained as follows:

H I v I O PCH 0 E 0 T 4 [236,6, -,trimethylcyclohexene 1')'- 3 11- CHI 0L1 CHI 9 2-methylbutene-(2)-al-(l) by glycide ester synthesis from B-ionone and chloroacetic ester and H30 CH3 CH2 treatment with alkali of the glycide ester formed 7 CIJLi (Isl'er et a l., Helvetica-Chimica Acta, volume 30, OH CH=C-CHCECC=CH a pageiwlni 7 2 55 I 3,8-dimethyldecadiene (3,7)-- dime-(1,9) is formed by dimerizing'l-bromo-3-methylpentene- I I (2 )-.yne-(4) by means of a Wurtz reaction. For

I condensation purposes, it is advantageous to eml ploy a :metal pain f or instance, a. Zn-Cu-pair, in

, place'oi pure zinc-: The compound boils'at 40- 3 -so c./o.oo mm; Hg: n =1.5o5 1; ultraviolet absorption maximum 230 m The condensation between 2 mols of 4-[2',6',6'-

trimethylcyclohexene (1') yl-l-2 -methylbutene-(2)-al-(1) and 1 mol of 3,8-dimethyldecadiene-(3,7)-diyne-(1,9) is efiected by metal-organic synthesis. Apart from the Grignard compound, the lithium-organic compound is particularly suitable. Ether, anisole, benzene, tolueneor xylene may serve as solvents. The hydrolysis of the salts of the condensation product formed can be effected by means of water, ammonium chlo- 3 grams of 3,8-dimethyldecadiene-(3,7) -diyne- (1,9) are dissolved in 50 cc. of absolute ether and cc. of an ethereal solution of lithium phenyl (containing 290 mg.==2.1 mol of lithium) are added. The milky solution is refluxed for 45 minutes. 12 grams of 4-[2',6,6-trimethylcyclohexene- (1') -yl] -2-methylbutene-(2) -al-(1), dissolved in 50 cc. of ether, are then added and heated to boiling for one hour. The solution thereby turns orange and becomes clear. After cooling down, the solution is poured onto a mixture of ice and OH: CH:

10 per cent. phosphoric acid, and the ether layer which has become almost colourless is washed neutral. After drying over sodium sulphate, the

c 4 tate separates which re-dis sclves upon addition of ether. After addition of 28 grams of 4-[2',6,6

trimethylcyclohexene- (1') yll -2-methy1butene- (2) -al-(1) the mixture is allowed to stand overnight and finally heated for an hour to 50 C.

The Grignard solution is thereupon decomposed with ice and 10 per cent. sulphuric acid, and the ether solution is well washed successively with sodium bicarbonate solution and water. After drying with sodium sulphate, the ether is evaporated and the toluene is distilled oif in vacuo.

33 grams of a dark oil remain behind as residue.

The excess 4-[2,6',6-trimethylcyclohexene- (1') -yll -2-methy1butene- (2) -al- (1) and lowmolecular by-products are distilled off in high vacuo at 10- mm. Hg and an airbath temper: ature of 90 C. The residue, which amounts to 14 grams, is dissolved in petroleum ether and purified chromatographically with the aid of aluminum oxide (Brockmann, activity grade III). 6.5 grams of a viscous oil with a molecular weight of 481 and-a maximal absorption in the ultra-violet ether isevaporated. 'The etherresidue forms a spectrum at 233 m are obtained as a middle fraction. The yield amounts to 36 per cent. of the theoretical quantity.

' We claim: I

' 1 Process for the manufacture of a condensation product with the carbon skeleton of B-carotene', comprising condensing 2 mole of 4- E2636- trimethylcyclohexene (1') -yl] -2methylbutene- (2) -al-(1) with a compound of the general formula Tom I out wherein X is selected from the group consisting of a lithium radical and a magnesium monobro mide radical; and hydrolyzing the resultingsalt of'the'gene'ral formulaz' I CH2 A CH:

2. Process according to claim 1,. comprisin effecting the condensation with the aid of lithium in ether and hydrolyzing with phosphoric acid.

3. Compounds of the general formula HaC CH5 I H: CH:

viscous oil which, for purification purposes, is distilled in a molecular still from a thin film at a pressure of 10- mm. Hg and at a temperature of 110 C. 10 grams of a. product having amolecular weight of 578 (calculated 570.87) and an ultraviolet absorption maximum of '233 m (e:21,000) remain behind as residue. The yield amounts to 93 per cent. of the theoretical quantity.

v I Example 2 A Grignard solution is preparedfrom 2.5 grams of magnesium and 10.3 grams of ethyl bromide. cc. of absolute toluene arezad'ed to this solution and the ether is evaporated in -vacuo. 5 grams of 3,8-dimethyldecadiene- (3,7) -diyne+ (1,9) are :addedto this Grignard solution and the mixture is heated to a bath temperature of 8030, for 30 minutes. -Whi1e standing '9. flaky iprecipi- CH: CH:

wherein X is selected from the group consisting of a lithium radical and a magnesium monobromide radical.

4. As a new compound: 1,18-di-[2,6',6'-trimethylcyclohexene (1') yl] 3,7,12,16-tetramethyl 4,15 dihydroxyoctadecatetraene (2,7,11,16) -diyne-(5,13).

HANS ERLOFF INHOFFEN. HORST POMMER.

REFERENCES CITED The following references are of record in the file of this patent:

Z. Vitamin-forsch, vol. 17, pages 88-97 (1946), abstracted in Chemical Abstracts, vol. 41, page 5600. 

3. COMPOUNDS OF THE GENERAL FORMULA 